INFLUENCE OF 5-HT3 RECEPTOR ANTAGONISTS AND THE INDIRECT 5-HT AGONIST, DEXFENFLURAMINE, ON HEROIN SELF-ADMINISTRATION IN RATS
INFLUENCE OF 5-HT3 RECEPTOR ANTAGONISTS AND THE INDIRECT 5-HT AGONIST, DEXFENFLURAMINE, ON HEROIN SELF-ADMINISTRATION IN RATS
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DOI：
10.1007/bf02244992
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发表时间：
1994-05-01
影响因子：
3.4
通讯作者：
SELLERS, EM
中科院分区：
文献类型：
--
作者：
HIGGINS, GA;WANG, YP;SELLERS, EM
本研究的目的是观察5-HT3拮抗剂恩丹西酮和MDL72222以及5-羟色胺释放剂和再摄取抑制剂右芬氟拉明对Wistar大鼠静脉注射海洛因的影响。使用不同的动物小组，使用两种不同的海洛因强化方案：根据FR5方案每天提供相对较低的剂量(每次0.03 mg/kg)，每天1小时；根据FR1方案，每天提供中等剂量(每次0.1 mg/kg)，每天2小时。在几天内获得稳定的反应水平后，纳洛酮(0.25 mg/kg SC)预处理和减半海洛因输注剂量都会增加每个浓度下对海洛因的操作剂反应。恩丹西酮(0.01~1 mg/kg SC)和MDL72222(0.1~3 mg/kg SC)对海洛因自身给药均无影响。恩丹西酮(0.01-0.1 mg/kg)慢性治疗(5天)同样无效。然而，右芬氟拉明(0.5-2.5毫克/千克IF)在剂量上持续减少海洛因的自我给药，仅产生轻微的食物反应下降。这些发现与位置条件作用研究相反，后者表明5-HT3拮抗剂而不是间接的5-羟色胺激动剂可以阻断吗啡诱导的位置偏爱。造成这种差异的原因仍有待确定。
The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01-1 mg/kg SC) nor MDL72222 (0.1-3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01-0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5-2.5 mg/kg IF) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.